Diabetic Ketoacidosis

Question 1

Diabetic ketoacidosis (DKA) is a life-threatening diabetic emergency.

Answer 1

DKA is a severe metabolic complication of diabetes. It is typically seen in those with T1DM as a presenting feature, in patients with poor control or intercurrent illness.

Hyperglycaemia results in osmotic diuresis and electrolyte abnormalities, which requires prompt recognition and management.

The condition is characterised by a biochemical triad of hyperglycaemia, ketonaemia and acidosis.

Hyperglycaemia: > 11.0 mmol/L or known DM
Ketonaemia: ≥ 3 mmol/L or significant ketonuria (> 2+ on dipstick)
Acidosis: bicarbonate < 15.0 mmol/L and/or venous pH < 7.3

Question 2

The condition is characterised by a biochemical triad of hyperglycaemia, ketonaemia and acidosis.

Answer 2

Hyperglycaemia: > 11.0 mmol/L or known DM
Ketonaemia: ≥ 3 mmol/L or significant ketonuria (> 2+ on dipstick)
Acidosis: bicarbonate < 15.0 mmol/L and/or venous pH < 7.3

Question 3

DKA represents an acute hyperglycaemic complication of diabetes that is common among type 1 diabetic patients.

Answer 3

The condition is being increasingly recognised in type 2 diabetes mellitus. This is discussed in more detail in ‘unusual presentations’.

It is suspected that 4% of patients with T1DM develop DKA each year and up to 14% of diabetes related hospital admissions are the result of DKA.

Question 4

The main precipitants of DKA are listed:

Answer 4

Infection: 30-40%
Non-compliance: 25%
Inappropriate dose alteration: 13%
New diagnosis of diabetes: 10-20%
Myocardial infarction: 1%

Question 5

Symptoms of DKA

Answer 5

Nausea
Vomiting
Polyuria
Polydipsia
Abdominal pain
Leg cramps
Headache

Question 6

Signs - DKA

Answer 6

Abdominal tenderness
Dehydration
Hypotension
Kussmaul breathing
Ketotic breath
Reduced consciousness
Coma

Question 7

The diagnosis of DKA is based on identification of the biochemical triad of …

Answer 7

The diagnosis of DKA is based on identification of the biochemical triad of hyperglycaemia, acidaemia and ketonaemia/ketonuria.

Question 8

Immediate investigations to establish diagnosis of DKA:

Answer 8

Laboratory glucose: > 11.0 mmol/L
Venous/arterial blood gas: pH < 7.3 or bicarbonate < 15 mmol/L
Ketone testing: capillary blood ketone ≥ 3 mmol/L or urinary ketones +++ or above

Question 9

Ketosis-prone T2DM

Answer 9

Some patients with T2DM are at risk of diabetic ketoacidosis. These patients are referred to as ketosis-prone. African Caribbean patients are particularly at risk. Therefore, acutely unwell patients with type 2 diabetes should always be assessed for DKA.

Question 10

Euglycaemic DKA

Answer 10

DKA is not always associated with hyperglycaemia. When DKA develops with normal or near-normal blood glucose levels it is referred to as euglycaemic DKA. This is important to recognise because it is associated with a higher mortality.

Euglycaemic DKA may occur in the presence of exhausted glycogen stores in the liver (e.g. protracted vomiting, alcohol use, malnutrition). An increasingly recognised cause of euglycaemic DKA is from the new anti-diabetic class sodium-glucose co-transporter-2 inhibitors (SGLT-2 inhibitors).

Question 11

Investigations

DKA

Answer 11

The main investigations in the management of DKA include a laboratory glucose, venous/arterial blood gas and a ketone measurement (blood/urine).

Question 12

DKA management

Answer 12

Patients presenting with DKA have a significant fluid deficit, are acidotic with high ketone and blood glucose levels, and high risk of electrolyte derangements.

Restore circulating volume and tissue perfusion
Clear serum/urinary ketones and halt ketogenesis
Decrease serum glucose towards a normal level
Correct electrolyte derangements
Identify and treat underlying precipitant

Question 13

Initial assessment DKA

Answer 13

Important aspects of the clinical assessment include a formal Glasgow coma score (GCS) and a full set of observations (HR, Temp, RR, BP, Sats). Concurrently, a series of initial investigations and interventions should be completed, which include:

Intravenous access (x2 large bore cannula)
Blood / urinary ketones
Capillary & plasma blood glucose
FBC, U&Es, venous blood gas (VBG)
Blood cultures
Urinalysis +/- MSU, Pregnancy test (as indicated)
ECG
Cardiac monitoring
Establish usual diabetic pharmacotherapy

Question 14

Severity

Assessment of severity is important to establish the level of care that patients require for ongoing management.

Answer 14

One or more of the following parameters would warrant referral to a high-dependency unit (level 2 care).

Blood ketone > 6 mmol/L
Bicarbonate level < 5 mmol/L
pH < 7.0
GCS ≤ 12
Systolic BP < 90 mmHg
Hypokalaemia on admission < 3.5 mmol/L

Question 15

Patients presenting with DKA will be intravascularly depleted with a significant fluid deficit requiring intravenous fluid replacement.

Answer 15

Fluid status should be assessed based on clinical and biochemical measurements. A urinary catheter may be required for more accurate monitoring.

The initial fluid of choice is 0.9% normal saline and patients should be given this immediately, especially in the presence of hypotension (Systolic BP < 90 mmHg). If the systolic BP does not improve with fluid (i.e > 90 mmHg), senior help should be sought and another cause for hypotension considered. The debate between 0.9% sodium chloride or another balanced crystalloid is ongoing in research.

Question 16

DKA fluid resus

Answer 16

A typical fluid regime for an average patient presenting with DKA would be a 1 litre of normal saline over 1 hour, followed by 2 litres each over 2 hours, followed by 2 litres each over 4 hours. At all times potassium replacement should be considered and patients fluid status regularly assessed for ongoing intravenous fluid needs. The typical water deficit in a patient with DKA is 100 ml/kg (i.e. up to 7 litres in a 70 kg person!).

Question 17

Potassium replacement DKA

Answer 17

Patients with DKA will be started on an intravenous insulin regime, which will decrease plasma potassium levels leading to profound hypokalaemia.

Question 18

Intravenous insulin therapy

Answer 18

Patients with established DKA need to be started on a fixed rate intravenous insulin infusion (FRIII) immediately, which is based on the patients weight (can be estimated).
Patients should be given a fixed infusion at 0.1 units/kg/hr. This means a 60 kg female will get an hourly rate of 6 units. The infusion is set up by mixing 50 units of short-acting insulin (ACTRAPID®) with 50 mls of 0.9% normal saline.

Question 19

Monitoring DKA

Answer 19

Patients should be monitored regularly to assess for an adequate fall in ketones, glucose and rise in bicarbonate with normalisation of acid-base balance.

Each hour, blood ketones and blood glucose should be checked. If the capillary blood glucose reading is greater than 20 or reporting ‘HI’, a formal blood glucose should be sent. A venous blood gas should be used for the pH and bicarbonate at 1 hour and 2 hours, and then 2 hours thereafter. Potassium should be checked as a minimum of every 4 hours within the first 24 hours, but sooner if abnormal.

In those with severe DKA, they should have continual cardiac and saturation monitoring. An accurate fluid balance should be kept and if urine output is not possible due to anuria or incontinence then a catheter should be considered.

Question 20

A number of metabolic treatment targets should be achieved during the management of DKA.

Answer 20

A number of metabolic treatment targets should be achieved during the management of DKA.
Blood ketones: falling by at least 0.5 mmol/L/h
Bicarbonate: rising by at least 3.0 mmol/L/h
Blood glucose: falling by at least 3.0 mmol/L/h
Serum potassium: maintain between 4.0 - 5.5 mmol/L

Question 21

Continuing care

DKA

Answer 21

The specialist diabetic team should always be informed regarding a presentation of DKA. Ideally, they should assess the patient within 24 hours.

Question 22

DKA (Resolving/)

Answer 22

Once DKA is resolved (blood ketones < 0.6 mmol/L and pH >7.3) and the patient is eating and drinking appropriately, they can be converted to subcutaneous insulin therapy. This process should ideally be managed by the specialist diabetic team. Importantly, conversion to subcutaneous should occur prior to stopping intravenous insulin (i.e. subcutaneous insulin with a meal then stopping intravenous insulin 1 hour later). If the patient is not eating and drinking, they can be converted to a variable rate intravenous insulin infusion (VRIII).

Question 23

Complications
DKA is an acute, life-threatening diabetic emergency that requires prompt and appropriate management to prevent adverse sequelae.

Answer 23

Mortality has improved significantly in the last 20 years to < 1%. However, DKA still accounts for high mortality in developing countries and non-hospitalised patients.

In the adult population, common causes of mortality include hypokalaemia, acute respiratory distress syndrome (ARDS) and co-morbid conditions such as sepsis or myocardial infarction. Other complications include cerebral oedema (more common in paediatric population) and hypoglycaemia.

Potassium disturbances are a significant issue in DKA. Severe dehydration can lead to pre-renal acute kidney injury and transmembrane shifts in potassium due to the ketoacidosis. These collectively lead to hyperkalaemia. However, on initiation of insulin therapy plasma potassium concentrations dramatically fall leading to dangerous hypokalaemia.